Methods and compositions for treating and preventing muscle wasting disorders

Abstract

Described herein are methods of treating and preventing muscle wasting and muscle loss, using adherent stromal cells and conditioned medium produced thereby.

What is claimed is: 
     
       1. A method of treating a Duchenne muscular dystrophy in a subject in need thereof, the method comprising administering to the subject adherent stromal cells (ASC), wherein said ASC: (i) originate from placenta tissue, (ii) are at least predominantly maternal cells, and (iii) have been cultured on a three-dimensional (3D) substrate, thereby treating the Duchenne muscular dystrophy. 
     
     
       2. The method of  claim 1 , further comprising the step of harvesting said ASC by removing said ASC from an apparatus where culturing on said 3D substrate was performed. 
     
     
       3. The method of  claim 1 , wherein culturing on said 3D substrate is performed in an apparatus that comprises a 3D bioreactor. 
     
     
       4. The method of  claim 1 , wherein culturing on said 3D substrate is performed in an apparatus that comprises a synthetic adherent material that is selected from the group consisting of a polyester, a polypropylene, a polyalkylene, a poly fluoro-chloro-ethylene, a polyvinyl chloride, a polystyrene, a polysulfone, a cellulose acetate, a glass fiber, a ceramic particle, a poly-L-lactic acid, and an inert metal fiber. 
     
     
       5. The method of  claim 1 , wherein said ASC have been incubated in a 2D adherent-cell culture apparatus prior to culturing on said 3D substrate. 
     
     
       6. The method of  claim 1 , wherein administering said ASC leads to one or more of the following: reduction of creatine phosphokinase levels in the subject, reduction of inflammation in a diaphragm of the subject, reduction of necrosis in a diaphragm of the subject, reduction of inflammation in quadriceps of the subject, or reduction of necrosis in quadriceps of the subject. 
     
     
       7. A method of reducing a loss of muscle mass in a subject with Duchenne muscular dystrophy, the method comprising administering to the subject adherent stromal cells (ASC), wherein said ASC: (i) originate from placenta tissue, (ii) are at least predominantly maternal cells, and (iii) have been cultured on a three-dimensional (3D) substrate, thereby reducing the loss of muscle mass in the subject with Duchenne muscular dystrophy. 
     
     
       8. The method of  claim 7 , further comprising the step of harvesting said ASC by removing said ASC from an apparatus where culturing on said 3D substrate was performed. 
     
     
       9. The method of  claim 7 , wherein culturing on said 3D substrate is performed in an apparatus that comprises a 3D bioreactor. 
     
     
       10. The method of  claim 7 , wherein culturing on said 3D substrate is performed in an apparatus that comprises a synthetic adherent material that is selected from the group consisting of a polyester, a polypropylene, a polyalkylene, a poly fluoro-chloro-ethylene, a polyvinyl chloride, a polystyrene, a polysulfone, a cellulose acetate, a glass fiber, a ceramic particle, a poly-L-lactic acid, and an inert metal fiber. 
     
     
       11. The method of  claim 7 , wherein said ASC have been incubated in a 2D adherent-cell culture apparatus prior to culturing on said 3D substrate. 
     
     
       12. The method of  claim 7 , wherein administering said ASC leads to one or more of the following: reduction of creatine phosphokinase levels in the subject, reduction of inflammation in a diaphragm of the subject, reduction of necrosis in a diaphragm of the subject, reduction of inflammation in quadriceps of the subject, or reduction of necrosis in quadriceps of the subject. 
     
     
       13. A method of treating muscle degeneration in a subject with Duchenne muscular dystrophy, the method comprising administering to the subject adherent stromal cells (ASC), wherein said ASC: (i) originate from placenta tissue, (ii) are at least predominantly maternal cells, and (iii) have been cultured on a three-dimensional (3D) substrate, thereby treating muscle degeneration in the subject with Duchenne muscular dystrophy. 
     
     
       14. The method of  claim 13 , further comprising the step of harvesting said ASC by removing said ASC from an apparatus where culturing on said 3D substrate was performed. 
     
     
       15. The method of  claim 13 , wherein culturing on said 3D substrate is performed in an apparatus that comprises a 3D bioreactor. 
     
     
       16. The method of  claim 13 , wherein culturing on said 3D substrate is performed in an apparatus that comprises a synthetic adherent material that is selected from the group consisting of a polyester, a polypropylene, a polyalkylene, a poly fluoro-chloro-ethylene, a polyvinyl chloride, a polystyrene, a polysulfone, a cellulose acetate, a glass fiber, a ceramic particle, a poly-L-lactic acid, and an inert metal fiber. 
     
     
       17. The method of  claim 13 , wherein said ASC have been incubated in a 2D adherent-cell culture apparatus prior to culturing on said 3D substrate. 
     
     
       18. The method of  claim 13 , wherein administering said ASC leads to one or more of the following: reduction of creatine phosphokinase levels in the subject, reduction of inflammation in a diaphragm of the subject, reduction of necrosis in a diaphragm of the subject, reduction of inflammation in quadriceps of the subject, or reduction of necrosis in quadriceps of the subject.